AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
{{expandStatus?'Exit ':''}}Advanced Search
In this study, combined analysis of expression profiling in the hippocampus of 76 patients with Alzheimer’s disease (AD) and 40 healthy controls was performed. The effects of covariates (including age, gender, postmortem interval, and batch effect) were controlled, and differentially expressed genes (DEGs) were identified using a linear mixed-effects model. To explore the biological processes, functional pathway enrichment and protein–protein interaction (PPI) network analyses were performed on the DEGs. The extended genes with PPI to the DEGs were obtained. Finally, the DEGs and the extended genes were ranked using the convergent functional genomics method. Eighty DEGs with q < 0.1, including 67 downregulated and 13 upregulated genes, were identified. In the pathway enrichment analysis, the 80 DEGs were significantly enriched in one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, GABAergic synapses, and 22 Gene Ontology terms. These genes were mainly involved in neuron, synaptic signaling and transmission, and vesicle metabolism. These processes are all linked to the pathological features of AD, demonstrating that the GABAergic system, neurons, and synaptic function might be affected in AD. In the PPI network, 180 extended genes were obtained, and the hub gene occupied in the most central position was CDC42. After prioritizing the candidate genes, 12 genes, including five DEGs (ITGB5, RPH3A, GNAS, THY1, and SEPT6) and seven extended genes (JUN, GDI1, GNAI2, NEK6, UBE2D3, CDC42EP4, and ERCC3), were found highly relevant to the progression of AD and recognized as promising biomarkers for its early diagnosis.
Bai Z, Han G, Xie B, Wang J, Song F, Peng X, Lei H, (2016) AlzBase: an integrative database for gene dysregulation in Alzheimer’s disease. Mol Neurobiol 53:310-319
Bates D, Machler M, Bolker BM, Walker SC, (2015) Fitting linear mixed-effects models using lme4. J Stat Softw 67:1-48
Bell KF, Ducatenzeiler A, Ribeiro-da-Silva A, Duff K, Bennett DA, Cuello AC, (2006) The amyloid pathology progresses in a neurotransmitter-specific manner. Neurobiol Aging 27:1644-1657
Berchtold NC, Cribbs DH, Coleman PD, Rogers J, Head E, Kim R, Beach T, Miller C, Troncoso J, Trojanowski JQ, Zielke HR, Cotman CW, (2008) Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci USA 105:15605-15610
Berchtold NC, Coleman PD, Cribbs DH, Rogers J, Gillen DL, Cotman CW, (2013) Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease. Neurobiol Aging 34:1653-1661
Blair LJ, Nordhues BA, Hill SE, Scaglione KM, O’Leary JC3rd, Fontaine SN, Breydo L, Zhang B, Li P, Wang L, Cotman C, Paulson HL, Muschol M, Uversky VN, Klengel T, Binder EB, Kayed R, Golde TE, Berchtold N, Dickey CA, (2013) Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. J Clin Investig 123:4158-4169
Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW, (2004) Incipient Alzheimer’s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 101:2173-2178
Chen K-D, Chang P-T, Ping Y-H, Lee H-C, Yeh C-W, Wang P-N, (2011) Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer’s disease. Neurobiol Dis 43:698-705
Cooper-Knock J, Kirby J, Ferraiuolo L, Heath PR, Rattray M, Shaw PJ, (2012) Gene expression profiling in human neurodegenerative disease. Nat Rev Neurol 8:518-530
da Huang W, Sherman BT, Lempicki RA, (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44-57
Fehlbaum-Beurdeley P, Prado ACJ-L, Pallares D, Carriere J, Soucaille C, Rouet F, Drouin D, Sol O, Jordan H, Wu D, Lei L, Einstein R, Schweighoffer F, Bracco L, (2010) Toward an Alzheimer’s disease diagnosis via high-resolution blood gene expression. Alzheimers Dement 6:25-38
Gao L, Gao H, Zhou H, Xu Y, (2013) Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson’s disease. BMC Neurol 13:181
Gueli MC, Taibi G, (2013) Alzheimer’s disease: amino acid levels and brain metabolic status. Neurol Sci 34:1575-1579
Hess JL, Tylee DS, Barve R, de Jong S, Ophoff RA, Kumarasinghe N, Tooney P, Schall U, Gardiner E, Beveridge NJ, Scott RJ, Yasawardene S, Perera A, Mendis J, Carr V, Kelly B, Cairns M, Neurobehavioural Genetics UnitTsuang MT, Glatt SJ, (2016) Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia. Schizophr Res 176:114-124
Hu W, Lin X, Chen K, (2015) Integrated analysis of differential gene expression profiles in hippocampi to identify candidate genes involved in Alzheimer’s disease. Mol Med Rep 12:6679-6687
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP, (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics (Oxford, England) 4:249-264
Karbalaei R, Allahyari M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Zali MR, (2018) Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterol Hepatol Bed Bench 11:27-33
Kuzirian MS, Paradis S, (2011) Emerging themes in GABAergic synapse development. Prog Neurobiol 95:68-87
Larsson O, Sandberg R, (2006) Lack of correct data format and comparability limits future integrative microarray research. Nat Biotechnol 24:1322-1323
Li G, Bien-Ly N, Andrews-Zwilling Y, Xu Q, Bernardo A, Ring K, Halabisky B, Deng C, Mahley RW, Huang Y, (2009) GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice. Cell Stem Cell 5:634-645
Li X, Long J, He T, Belshaw R, Scott J, (2015) Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer’s disease. Sci Rep 5:12393
Li Y, Sun H, Chen Z, Xu H, Bu G, Zheng H, (2016) Implications of GABAergic neurotransmission in Alzheimer’s disease. Front Aging Neurosci 8:331
Li T, Wernersson R, Hansen RB, Horn H, Mercer J, Slodkowicz G, Workman CT, Rigina O, Rapacki K, Staerfeldt HH, Brunak S, Jensen TS, Lage K, (2017) A scored human protein-protein interaction network to catalyze genomic interpretation. Nat Methods 14:61-64
Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Ramsey K, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette CM, Schmechel D, Reiman EM, Rogers J, Stephan DA, (2008) Altered neuronal gene expression in brain regions differentially affected by Alzheimer’s disease: a reference data set. Physiol Genomics 33:240-256
Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Niedzielko TL, Schneider LE, Mastroeni D, Caselli R, Kukull W, Morris JC, Hulette CM, Schmechel D, Rogers J, Stephan DA, (2008) Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci USA 105:4441-4446
Maes OC, Xu S, Yu B, Chertkow HM, Wang E, Schipper HM, (2007) Transcriptional profiling of Alzheimer blood mononuclear cells by microarray. Neurobiol Aging 28:1795-1809
Mak E, Gabel S, Su L, Williams GB, Arnold R, Passamonti L, Vazquez Rodriguez P, Surendranathan A, Bevan-Jones WR, Rowe JB, O’Brien JT, (2017) Multi-modal MRI investigation of volumetric and microstructural changes in the hippocampus and its subfields in mild cognitive impairment, Alzheimer’s disease, and dementia with Lewy bodies. Int Psychogeriatr 29:545-555
Marttinen M, Kurkinen KM, Soininen H, Haapasalo A, Hiltunen M, (2015) Synaptic dysfunction and septin protein family members in neurodegenerative diseases. Mol Neurodegener 10:16
Mirza Z, Kamal MA, Buzenadah AM, Al-Qahtani MH, Karim S, (2014) Establishing genomic/transcriptomic links between Alzheimer’s disease and type 2 diabetes mellitus by meta-analysis approach. CNS Neurol Disord-Drug Targets 13:501-516
Nateri AS, Riera-Sans L, Da Costa C, Behrens A, (2004) The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science (New York, NY) 303:1374-1378
Nilsen LH, Rae C, Ittner LM, Gotz J, Sonnewald U, (2013) Glutamate metabolism is impaired in transgenic mice with tau hyperphosphorylation. J Cereb Blood Flow Metab 33:684-691
Paquet C, Nicoll JA, Love S, Mouton-Liger F, Holmes C, Hugon J, Boche D, (2017) Downregulated apoptosis and autophagy after anti-Abeta immunotherapy in Alzheimer’s disease. Brain Pathol 28(5):603-610
Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, Sheppard D, Hynes RO, Hodivala-Dilke KM, (2002) Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8:27-34
Rosenberg PB, Nowrangi MA, Lyketsos CG, (2015) Neuropsychiatric symptoms in Alzheimer’s disease: What might be associated brain circuits? Mol Aspects Med 43–44:25-37
Smith R, Klein P, Koc-Schmitz Y, Waldvogel HJ, Faull RL, Brundin P, Plomann M, Li JY, (2007) Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington’s disease. J Neurochem 103:115-123
Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, Phillips BE, Cederholm T, Jensen T, van Loon LJ, Lannfelt L, Kraus WE, Atherton PJ, Howard R, Gustafsson T, Hodges A, Timmons JA, (2015) A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status. Genome Biol 16:185
Storey JD, Tibshirani R, (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci USA 100:9440-9445
Sun B, Halabisky B, Zhou Y, Palop JJ, Yu G, Mucke L, Gan L, (2009) Imbalance between GABAergic and glutamatergic transmission impairs adult neurogenesis in an animal model of Alzheimer’s disease. Cell Stem Cell 5:624-633
van Cauwenberghe C, van Broeckhoven C, Sleegers K, (2016) The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 18:421-430
Wang J, Qu S, Wang W, Guo L, Zhang K, Chang S, Wang J, (2016) A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex. J Psychiatr Res 82:23-29
Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, De Luca GC, Crary JF, Casaccia P, Buxbaum JD, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B, (2016) Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease. Genome Med 8:104
Wang Z, Wang Z, Zhou Z, Ren Y, (2016) Crucial genes associated with diabetic nephropathy explored by microarray analysis. BMC Nephrol 17:128
Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Clifford RM, Jagust W, Morris JC, Petersen RC, Saykin AJ, Shaw LM, Toga AW, Trojanowski JQ, Alzheimer’s Dis N, (2017) Recent publications from the Alzheimer’s disease neuroimaging initiative: reviewing progress toward improved AD clinical trials. Alzheimers Dement 13:E1-E85
Wilson CL, Miller CJ, (2005) Simpleaffy: a BioConductor package for affymetrix quality control and data analysis. Bioinformatics 21:3683-3685
Xu M, Zhang DF, Luo R, Wu Y, Zhou H, Kong LL, Bi R, Yao YG, (2018) A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer’s disease. Alzheimers Dement 14:215-229
Zhou C, Martinez E, Di Marcantonio D, Solanki-Patel N, Aghayev T, Peri S, Ferraro F, Skorski T, Scholl C, Frohling S, Balachandran S, Wiest DL, Sykes SM, (2017) JUN is a key transcriptional regulator of the unfolded protein response in acute myeloid leukemia. Leukemia 31:1196-1205
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
京公网安备11010802044758号